Although many pontentially harmful substances are introduced into the oral cavity or produced there by the local flora, little is known about the permeability of oral mucosa. Such information appears essential for the understanding of pathologic conditions such as peridontal disease, oral ulceration and oral carcinoma, all of which may be initiated or sustained by agents entering through the epithelial surface. The proposed study will first examine and compare the permeability of normal keratinized and non-keratinized oral epithelium and epidermis then examine the chemical nature of the permeability barrier, and finally consider the effects of mechanical trauma (friction), chemical trauma and the ensuing hyperplasia and inflammation on permeability. The principal methods of investigation will involve the use of morphological tracers to localize penetration pathways and determine the location of permeability barriers in vivo with electron microscopy. Results obtained by this approach will be compared with data from experiments determining the total flux of the same tracers across oral epithelium in vitro and with the localization demonstrated in unfixed tissue using the electron microprobe. Susequently the chemical nature of the permeability barrier will be studied by selective enzyme digestion, prior to using the tracers as probes for changes in permeability arising as a consequence of specific enzyme action. The final experiments will examine the effects of trauma on permeability to the morphological tracers.